Field of the Invention
The present invention relates generally to the fields of treatment and prevention of influenza virus infections using antibodies or fragments thereof. More particularly, it relates to the development of monoclonal antibodies for use in the diagnosis, prevention and treatment of H1N1 infections.
Background
When an infection breaks out, finding an effective treatment or prevention in a timely manner is critical in order to control the spread of the disease. The urgency of finding effective treatments is highlighted by recent outbreaks, such as the H1N1 outbreak of 2009.
The 2009 H1N1 influenza outbreak inflicted more than 60 million patients and more than a quarter million required hospitalization. The 2009 H1N1 pandemic influenza virus, which is designated as A(H1N1)pdm09 by WHO, disproportionally caused severe syndromes in young children and the elderly.
The highly infectious nature of H1N1 prompted an unusually swift and intense effort to find a vaccine to prevent further spread of this illness. Due to this intense effort, an effective H1N1 vaccine, PANFLU.1, became available five months after the outbreak. This vaccine was effective in inducing immune responses in more than 90% of people aged between 12 and 60 years old. However, this vaccine was less effective in children and elderly and was ineffective in people with compromised immune system.
To have an effective counter measure during an outbreak, it is important to have passive immunotherapy to provide immediate protection. In addition, passive immunotherapy can also be used to treat infected individuals. Passive immunotherapies require antibodies that are effective in the preventing infection by the infectious agents. Such antibodies may be developed using various technologies, typically using a virus-derived antigen or an inactivated virus to induce antibodies in a suitable subject. In addition, such antibodies may be isolated from patients who had been infected by the virus and have since recovered from the illness.
For example, Hao Wang et al. (Cellular & Molecular Immunology, (2013) 10, 403-412) discloses an approach for screening viral neutralizing monoclonal antibodies (mAbs) from individuals vaccinated with the 2009 pandemic H1N1 vaccine PANFLU.1. Specifically, B cells from immunized individuals were isolated and immortalized by fusion with Epstein-Barr virus (EBV). The Epstein-Barr virus (EBV)-immortalized memory B cells were screened. From this screening, seven mAbs were identified with both high viral neutralizing capacities and hemagglutination inhibition (HAI) activities against the 2009 pandemic H1N1 viruses. These mAbs may be used for passive immunotherapy of infected patients.
While screening from memory B cells derived from donors vaccinated with a specific antigen can provide useful monoclonal antibodies against H1N1, there is still a need for better antibodies for the prevention and treatment of influenza infections (e.g., H1N1 infection).